Inflammatory mechanisms are very important for the innate defence system of the body. When the host body encounters stimuli it perceives as harmful, such as pathogens and/or products thereof, injured cells or tissue, or any foreign object that irritates the surrounding tissue, the host often responds with a complex generalized response. A part of this response involves vascular tissues, leading to increased translocation of circulating white blood cells (WBC or leukocytes), especially the granule-containing cells (such as neutrophils) and mononuclear cells (such as monocytes), as well as plasma (containing necessary proteins, such as fibrin, complements, and immunoglobulins, a.k.a. antibodies), from blood to the area of injury. This process is known as inflammation.

There are many players in this, including immune defense cells already resident in the tissue; they secrete certain biochemical mediators (e.g. ‘cytokines’, ‘chemokines’, ‘prostaglandins’ and so forth), that initiate various biochemical events and act as beacons for the migrating leukocytes to home in on. The first batch of leukocytes would themselves secrete more of such mediators, in order to call in reinforcements. This is how the inflammatory response matures, involving the local vascular system, the immune system, and various cells at the site of injury.

What do these inflammatory immune cells do? These cells, now called ‘Effectors’, are able to kill the offending pathogens, destroy the remnants of injured cells or tissue, break down or bury the foreign object, so that the healing process can begin. Several non-cellular processes, associated with the plasma proteins, help inititate and propagate this inflammatory process, also taking part in healing.

Inflammation can be classified temporally as (a) acute – a short term process that often initiates within minutes or hours following injury and subsides upon resolution of the injury, or (b) chronic – a prolonged process in which inflammatory cells may progressively shift to the site of injury even after the deleterious stimulus is gone, causing persistent destruction of tissue.

Superficial acute inflammation, such as on the skin, may be observed as a zone of redness, hot to touch, prone to swelling, and often, tender. This is what happens after, say, an insect bite, frostbite, skin contact with plants such as Poison Ivy, or immune reactions due to hypersensitivity to certain medicines (e.g. metronidazole, an antibiotic, causes me to break out in hives; some allergic responses can cause inflammation of the airways, leading to respiratory distress). However, inflammation can equally occur in internal organs, and may cause a pain sensation when it reaches those areas that contain nociceptors (pain-sensitive nerve endings). This is how various non-steroidal anti-inflammatory drugs work; they reduce pain by inhibiting various molecules that are responsible for inflammation.

Chronic inflammation, on the other hand, is considered responsible for a large variety of unrelated human diseases, ranging from immune system disorders that cause unmitigated, exuberant inflammation – such as observed in allergic reactions; inflammatory injury to muscles (myopathies) or to various organ systems (e.g. inflammatory bowel diseases, pelvic inflammatory disease, and glomerulonephritis); various autoimmune disorders, and so forth; to non-immune diseases, such as certain cancers, atherosclerosis and ischemic heart disease.

As a student of host-pathogen interaction, I encounter inflammation from that specific context, but the principle remains generalizable. This concept has been nicely laid out in the Damage Response Framework of Microbial Pathogenesis proposed by Casadevall and Pirofski in 2003.1 One of the mechanisms by which microbe-induced damage is caused to the host tissue is inflammation, i.e. immune-mediated damage. Virulence (i.e. the ability to cause disease) of various bacterial, fungal and parasitic pathogens is often paralleled by their ability to incite various profiles of inflammation. For example (all from Ref. 1),

The etiological agent of tuberculosis, Mycobacterium tuberculosis, is a pathogen that causes disease in two ways: in immunocompromised individuals (such as HIV+ people), the host doesn’t mount an adequate response. Interestingly, in immune-sufficient individuals, the damage is mediated by a robust inflammatory response that the host generates against the bug.

A mutant of everyone’s beloved yeast, Saccharomyces cerevisiae, that has altered surface properties capable of eliciting a strong inflammatory response, is virulent in mice.

Lung damage in AIDS patients from pneuomonia induced by Pneumocystis carinii is mediated largely by the residual immune system, which is likely why corticosteroid-induced specific suppression of inflammation leads to better outcomes in patients.

The mold pathogen, Aspergillus fumigatus, causes disease in individuals with weak or strong immunity, and in the latter, the disease takes the form of exuberant inflammatory response and hypersensitivity reactions to Aspergillus antigens.

Neurocysticercosis, a debilitating neurological disorder, occurs when the host mounts a strong inflammatory response to the worm parasite Taenia solium, even if the worm is dead.

Therefore, evidently, inflammation is a two-edged sword, requiring a fine balance between initiation and termination, in order to promote health and not disease.